Circadian rhythm disturbance in agitation of Alzheimer's disease

Abstract

AbstractBackgroundAgitation in Alzheimer’s Disease (Agit‐AD) is a major cause of burden for caregivers and may be driven by disrupted circadian rhythms and sleep. The circadian clock that generates these rhythms regulates patterns in mood, wakefulness, and other physiologic processes, such as body temperature and hormone levels. This project aims to examine if agitated AD subjects (AgitAD+) exhibit delayed circadian phase and lower rhythm strength compared to non‐agitated AD subjects (AgitAD‐) and healthy controls. We will additionally compare sleep amount, sleep quality, and degree of sleep disordered breathing among AgitAD+ vs. AgitAD‐ and healthy controls.MethodParticipants completed wrist actigraphy for one week to quantify rest/activity rhythms and sleep; consumed an ingestible, disposable temperature sensor for 1‐2 days to quantify core body temperature rhythms; and completed a single night of home sleep testing (HST). Inclusion criteria were diagnosis of AD and age 55‐90 years, and exclusion criteria include seizures, significant tremors, delirium, CPAP use for sleep apnea, restless legs syndrome, and circadian rhythm disorders. Due to the COVID‐19 pandemic, we implemented hybrid visits with telemedicine to limit in‐person interactions.ResultTo date, 26 participants have enrolled. There were no statistically significant differences observed in actigraphic sleep parameters between groups (Table 1). However, AgitAD+ participants had lower levels of activity in the morning and greater activity in the afternoon and evening (Figure 1). After adjustment for age, agitation was associated with lower activity in the morning and a trend towards greater activity in the afternoon and evening (Figure 2). This preliminary finding may suggest that AgitAD+ participants express lower and delayed activity rhythms. HST results show a trend toward less REM sleep and longer initial REM latency in the AgitAD+ group (Table 2). Updated results will be presented at AAIC (estimated 6‐10 additional participants).ConclusionThis study could provide evidence for CRD/sleep disturbance as a driver of Agit‐AD and could identify Agit‐AD subtypes who are most likely to from chronobiotic or sleep interventions.